Female pseudohermaphroditism associated with a novel homozygous G-to-A (V370-to-M) substitution in the P-450 aromatase gene.

The conversion of C19 androgens to their corresponding C18 estrogens is catalyzed by an enzyme complex known as aromatase. P-450 aromatase is expressed in a tissue-specific manner and placental deficiency abolishes its function in protecting the female fetus from masculinization and the mother from prepartum virilization due to an excess of androgens. Here we report a novel homozygous aromatase mutation (Val370-to-Met) found in a girl with pseudohermaphroditism (Prader V). Sequence analysis showed the parents to be heterozygous for this amino acid substitution. Since P-450arom deficiency is a rare autosomally recessive transmitted disease, consanguinity in this kindred seemed to be obvious. With the characterization of four intragenic polymorphisms and subsequent haplotype analysis this assumption turned out to be most likely.